Multiple Sclerosis

Gale Encyclopedia of Medicine, 3rd ed.
COPYRIGHT 2006 Thomson Gale

Multiple Sclerosis

Definition

Multiple sclerosis (MS) is a chronic autoimmune disorder affecting movement, ensation, and bodily functions. It is caused by destruction of the myelin insulation covering nerve fibers (neurons) in the central nervous system (brain and spinal cord).

Description

MS is a nerve disorder caused by destruction of the insulating layer surrounding neurons in the brain and spinal cord. This insulation, called myelin, helps electrical signals pass quickly and smoothly between the brain and the rest of the body. When the myelin is destroyed, nerve messages are sent more slowly and less efficiently. Patches of scar tissue, called plaques, form over the affected areas, further disrupting nerve communication. The symptoms of MS occur when the brain and spinal cord nerves no longer communicate properly with other parts of the body. MS causes a wide variety of symptoms and can affect vision, balance, strength, sensation, coordination, and bodily functions.

Multiple sclerosis affects more than a quarter of a million people in the United States. Most people have their first symptoms between the ages of 20 and 40; symptoms rarely begin before 15 or after 60. Women are almost twice as likely to get MS as men, especially in their early years. People of northern European heritage are more likely to be affected than people of other racial backgrounds, and MS rates are higher in the United States, Canada, and Northern Europe than in other parts of the world. MS is very rare among Asians, North and South American Indians, and Eskimos.

Causes and symptoms

Causes

Multiple sclerosis is an autoimmune disease, meaning its cause is an attack by the body's own immune system. For unknown reasons, immune cells attack and destroy the myelin sheath that insulates neurons in the brain and spinal cord. This myelin sheath, created by other brain cells called glia, speeds transmission and prevents electrical activity in one cell from short-circuiting to another cell. Disruption of communication between the brain and other parts of the body prevent normal passage of sensations and control messages, leading to the symptoms of MS. The demyelinated areas appear as plaques, small round areas of gray neuron without the white myelin covering. The progression of symptoms in MS is correlated with development of new plaques in the portion of the brain or spinal cord controlling the affected areas. Because there appears to be no pattern in the appearance of new plaques, the progression of MS can be unpredictable.

Despite considerable research, the trigger for this autoimmune destruction is still unknown. At various times, evidence has pointed to genes, environmental factors, viruses, or a combination of these.

The risk of developing MS is higher if another family member is affected, suggesting the influence of genetic factors. In addition, the higher prevalence of MS among people of northern European background suggests some genetic susceptibility.

The role of an environmental factor is suggested by studies of the effect of migration on the risk of developing MS. Age plays an important role in determining this change in risk—young people in low-risk groups who move into countries with higher MS rates display the risk rates of their new surroundings, while older migrants retain the risk of their original home country. One interpretation of these studies is that an environmental factor, either protective or harmful, is acquired in early life; the risk of disease later in life reflects the effects of the early environment.

These same data can be used to support the involvement of a slow-acting virus, one that is acquired early on but begins its destructive effects much later. Slow viruses are known to cause other diseases, including AIDS. In addition, viruses have been implicated in other autoimmune diseases. Many claims have been made for the role of viruses, slow or otherwise, as the trigger for MS, but as of 2001 no strong candidate has emerged.

How a virus could trigger the autoimmune reaction is also unclear. There are two main models of virally induced autoimmunity. The first suggests the immune system is actually attacking a virus (one too well-hidden for detection in the laboratory), and the myelin damage is an unintentional consequence of fighting the infection. The second model suggests the immune system mistakes myelin for a viral protein, one it encountered during a prior infection. Primed for the attack, it destroys myelin because it resembles the previously-recognized viral invader.

Either of these models allows a role for genetic factors, since certain genes can increase the likelihood of autoimmunity. Environmental factors as well might change the sensitivity of the immune system or interact with myelin to provide the trigger for the secondary immune response. Possible environmental triggers that have been invoked in MS include viral infection, trauma, electrical injury, and chemical exposure, although controlled studies do not support a causative role.

Symptoms

The symptoms of multiple sclerosis may occur in one of three patterns:

The most common pattern is the "relapsing-remitting" pattern, in which there are clearly defined symptomatic attacks lasting 24 hours or more, followed by complete or almost complete improvement. The period between attacks may be a year or more at the beginning of the disease, but may shrink to several months later on. This pattern is especially common in younger people who develop MS.

In the "primary progressive" pattern, the disease progresses without remission or with occasional plateaus or slight improvements. This pattern is more common in older people.

In the "secondary progressive" pattern, the person with MS begins with relapses and remissions, followed by more steady progression of symptoms.

Between 10-20% of people have a benign type of MS, meaning their symptoms progress very little over the course of their lives.

Because plaques may form in any part of the central nervous system, the symptoms of MS vary widely from person-to-person and from stage-to-stage of the disease. Initial symptoms often include:

Muscle weakness, causing difficulty walking

Loss of coordination or balance

Numbness, "pins and needles," or other abnormal sensations

Visual disturbances, including blurred or double vision.

Later symptoms may include:

Fatigue

Muscle spasticity and stiffness

Tremors

Paralysis

Pain

Vertigo

Speech or swallowing difficulty

Loss of bowel and bladder control

Incontinence, constipation

Sexual dysfunction

Cognitive changes.

Weakness in one or both legs is common, and may be the first symptom noticed by a person with MS. Muscle spasticity, or excessive tightness, is also common and may be more disabling than weakness.

Double vision or eye tremor (nystagmus ) may result from involvement of the nerve pathways controlling movement of the eye muscles. Visual disturbances result from involvement of the optic nerves (optic neutritis) and may include development of blind spots in one or both eyes, changes in color vision, or blindness. Optic neuritis usually involves only one eye at a time and is often associated with movement of the effected eye.

More than half of all people affected by MS have pain during the course of their disease, and many experience chronic pain, including pain from spasticity. Acute pain occurs in about 10% of cases. This pain may be a sharp, stabbing pain especially in the face, neck, or down the back. Facial numbness and weakness are also common.

Cognitive changes, including memory disturbances, depression, and personality changes, are found in people affected by MS, though it is not entirely clear whether these changes are due primarily to the disease or to the psychological reaction to it. Depression may be severe enough to require treatment in up to 25% of those with MS. A smaller number of people experience disease-related euphoria, or abnormally elevated mood, usually after a long disease duration and in combination with other psychological changes.

Symptoms of MS may be worsened by heat or increased body temperature, including fever, intense physical activity, or exposure to sun, hot baths, or showers.

Diagnosis

There is no single test that confirms the diagnosis of multiple sclerosis, and there are a number of other diseases with similar symptoms. While one person's diagnosis may be immediately suggested by her symptoms and history, another's may not be confirmed without multiple tests and prolonged observation. The distribution of symptoms is important: MS affects multiple areas of the body over time. The pattern of symptoms is also critical, especially evidence of the relapsing- remitting pattern, so a detailed medical history is one of the most important parts of the diagnostic process. A thorough search to exclude other causes of a patient's symptoms is especially important if the following features are present: 1) family history of neurologic disease, 2) symptoms and findings attributable to a single anatomic location, 3) persistent back pain, 4) age of onset over 60 or under 15 years of age, or 5) progressively worsening disease.

In addition to the medical history and a standard neurological exam, several lab tests are used to help confirm or rule out a diagnosis of MS:

Magnetic resonance imaging (MRI) can reveal plaques on the brain and spinal cord. Gadolinium enhancement can distinguish between old and new plaques, allowing a correlation of new plaques with-new symptoms. Plaques may be seen in several other-diseases as well, including encephalomyelitis, neurosarcoidosis, and cerebral lupus. Plaques on MRI may be difficult to distinguish from small strokes, areas of decreased blood flow, or changes seen with trauma or normal aging.

A lumbar puncture, or spinal tap, is done to measure levels of immune proteins, which are usually elevated in the cerebrospinal fluid of a person with MS. This test may not be necessary if other tests are diagnostic.

Evoked potential tests, electrical tests of conduction speed in the nerves, can reveal reduced speeds consistent with the damage caused by plaques. These tests may be done with small electrical charges applied to the skin (somatosensory evoked potential), with light patterns flashed on the eyes (visual evoked potential), or with sounds presented to the ears (auditory evoked potential).

The clinician making the diagnosis, usually a neurologist, may classify the disease as "definite MS," meaning the symptoms and test results all point toward MS as the cause. "Probable MS" and "possible MS" reflect less certainty and may require more time to pass to observe the progression of the disease and the distribution of symptoms.

Treatment

The three major drugs previously approved for the treatment of MS affect the course of the disease. None of these drugs is a cure, but they can slow disease progression in many patients.

Known as the ABC drugs, Avonex and Betaseron are forms of the immune system protein beta interferon, while Copaxone is glatiramer acetate (formerly called copolymer-1). All three have been shown to reduce the rate of relapses in the relapsing-remitting form of MS. Different measurements from tests of each have demonstrated other benefits as well: Avonex may slow the progress of physical impairment, Betaseron may reduce the severity of symptoms, and Copaxone may decrease disability. All three drugs are administered by injection

Two major clinical studies were recently completed that focused on the question of whether disease-modifying therapy known to slow the disease, can postpone the development of clinically definitive MS in high risk patients. Data presented at the annual meeting of the American Academy of Neurology in May, 2000, highlighted the different effects of interferon therapy when it was initiated at the earliest recognizable stages of MS versus later. Previous studies with interferon beta-1b (Betaseron) and interferon beta-1a (Avonex, Rebif) clearly demonstrated benefits in patients with relapsing forms of MS. Moreover, previous treatment with High-dose corticosteroids also delays, but does not prevent the ultimate development of MS. The encouraging message from the CHAMPS study in the United states and the ETOMS study in Europe is that early intervention can reduce the probability of developing clinically definitive MS.

Although the ABC drugs stop relapses and may keep patients in relatively good health for the short-term, their long-term success has not been proven and they don't work well for patients who have reached a steadily progressive stage of MS. In the meantime, new approaches to using current therapies are being researched especially using combinations of different types of agents when one agent alone is not effective. Clinical trials are now evaluating the safety and efficacy of combining cyclophosphamide (Cytoxan) and methylprednisolone (Medrol) in patients who do not respond to the ABC drus, and of adding mitoxantrone (Novantrone), prednisone (Prelone), azathioprine (Imuran), or methotrexate (Rheumatrex) to betainterferon for further benefit.

In addition, Miloxzantrone HCI (novantrone), a drug approved for cancer treatment, has been approved for treating patients with advanced or chronic multiple scelereosis.In clinical trials, mitoxantrone reduced the number of relapse episodes and slowed down the disease. Reserved for progressive forms of MS, it is given intravenously by a doctor to help maintain mobility and reduce the number of flare-ups. However, there are serious side effects with the drug including heart problems, nausea, and hair thinning.

As reported in the Spring, 2001, Volume 19, No 2 issue of InsideMS, the FDA recently approved the Copaxone Autoject and the Mixject vial adapters to help people using Copaxone self administer the drug. The autoject keeps the syringe steady and hides the needle. The same syringe may be used for both mixing and injecting with the Mixject vial adapters. A similar device is available for patients using Betassseron. Some patients are using the needlefree Biojector 2000 which uses a CO2 cartridge to deliver doses of medication through the skin. The FDA has not approved its use and patients should discuss this with their physician for its use with either Copaxone or Betaseron. Avonex must be injected in the muscle.

Immunosuppressant drugs have been used for many years to treat acute exacerbations (relapses). Drugs used include corticosteroids such as prednisone and methylprednisone; the hormone adrenocorticotropic hormone (ACTH); and azathioprine. Recent studies indicate that several days of intravenous methylprednisone may be more effective than other immunosuppressant treatments for acute symptoms. This treatment may require hospitalization.

MS causes a large variety of symptoms, and the treatments for these are equally diverse. Most symptoms can be treated and complications avoided with good care and attention from medical professionals. Good health and nutrition remain important preventive measures. Vaccination against influenza can prevent respiratory complications, and contrary to earlier concerns, is not associated with worsening of symptoms. Preventing complications such as pneumonia, bed sores, injuries from falls, or urinary infection requires attention to the primary problems which may cause them. Shortened life spans with MS are almost always due to complications rather than primary symptoms themselves.

Physical therapy helps the person with MS to strengthen and retrain affected muscles; to maintain range of motion to prevent muscle stiffening; to learn to use assistive devices such as canes and walkers; and to learn safer and more energy-efficient ways of moving, sitting, and transferring. Exercise and stretching programs are usually designed by the physical therapist and taught to the patient and caregivers for use at home. Exercise is an important part of maintaining function for the person with MS. Swimming is often recommended, not only for its low-impact workout, but also because it allows strenuous activity without overheating.

Occupational therapy helps the person with MS adapt to her environment and adapt the environment to her. The occupational therapist suggests alternate strategies and assistive devices for activities of daily living, such as dressing, feeding, and washing, and evaluates the home and work environment for safety and efficiency improvements that may be made.

Training in bowel and bladder care may be needed to prevent or compensate for incontinence. If the urge to urinate becomes great before the bladder is full, some drugs may be helpful, including propantheline bromide (Probanthine), oxybutynin chloride (Ditropan), or imipramine (Tofranil). Baclofen (Lioresal) may relax the sphincter muscle, allowing full emptying. Intermittent catheterization is effective in controlling bladder dysfunction. In this technique, a catheter is used to periodically empty the bladder.

Spasticity can be treated with oral medications, including baclofen and diazepam (Valium), or by injection with botulinum toxin (Botox). Spasticity relief may also bring relief from chronic pain. Other more acute types of pain may respond to carbamazepine (Tegretol) or diphenylhydantoin (Dilantin). Low back pain is common from increased use of the back muscles to compensate for weakened legs. Physical therapy and over-the-counter pain relievers may help.

Fatigue may be partially avoidable with changes in the daily routine to allow more frequent rests. Amantadine (Symmetrel) and pemoline (Cylert) may improve alertness and lessen fatigue. Visual disturbances often respond to corticosteroids. Other symptoms that may be treated with drugs include seizures, vertigo, and tremor.

Myloral, an oral preparation of bovine myelin, has recently been tested in clinical trials for its effectiveness in reducing the frequency and severity of relapses. Preliminary data indicate no difference between it and placebo.

Alternative treatment

Bee venom has been suggested as a treatment for MS, but no studies or objective reports support this claim.

In British studies, marijuana has been shown to have variable effects on the symptoms of MS. Improvements have been documented for tremor, pain, and spasticity, and worsening for posture and balance. Side effects have included weakness, dizziness, relaxation, and incoordination, as well as euphoria. As a result, marijuana is not recommended as an alternative treatment.

Some studies support the value of high doses of vitamins, minerals, and other dietary supplements for controlling disease progression or improving symptoms. Alpha-linoleic and linoleic acids, as well as selenium and vitamin E, have shown effectiveness in the treatment of MS. The selenium and vitamin E act as antioxidants. In addition, the Swank diet (low in saturated fats), maintained over a long period of time, may retard the disease process.

Removal of mercury fillings has been touted as a possible cure, but is of no proven benefit.

Studies have also shown that t'ai chi can be an effective therapy for MS because it works to improve balance and increase strength.

There are conflicting views about Echinacea and its benefit to MS. Some medicine books recommend Echinacea for people with MS. However, Echinacea appears to stimulate different parts of the immune system, particularly immune cells known as macrophages. In MS these cells are very active already and further stimulation could worsen the disease.

Prognosis

It is difficult to predict how multiple sclerosis will progress in any one person. Most people with MS will be able to continue to walk and function at their work for many years after their diagnosis. The factors associated with the mildest course of MS are being female, having the relapsing-remitting form, having the first symptoms at a younger age, having longer periods of remission between relapses, and initial symptoms of decreased sensation or vision rather than of weakness or incoordination.

Less than 5% of people with MS have a severe progressive form, leading to death from complications within five years. At the other extreme, 10-20% have a benign form, with a very slow or no progression of their symptoms. The most recent studies show that about seven out of 10 people with MS are still alive 25 years after their diagnosis, compared to about nine out of 10 people of similar age without disease. On average, MS shortens the lives of affected women by about six years, and men by 11 years. Suicide is a significant cause of death in MS, especially in younger patients.

The degree of disability a person experiences five years after onset is, on average, about three-quarters of the expected disability at 10-15 years. A benign course for the first five years usually indicates the disease will not cause marked disability.

Prevention

There is no known way to prevent multiple sclerosis. Until the cause of the disease is discovered, this is unlikely to change. Good nutrition; adequate rest; avoidance of stress, heat, and extreme physical exertion; and good bladder hygiene may improve quality of life and reduce symptoms.

Resources

BOOKS

KEY TERMS

Clinical trial— All new drugs undergo clinical trials before approval. Clinical trials are carefully conducted tests in which effectiveness and side effects are studied, with the placebo effect eliminated.

Evoked potentials— Tests that measure the brain's electrical response to stimulation of sensory organs (eyes or ears) or peripheral nerves (skin). These tests may help confirm the diagnosis of multiple sclerosis.

Myelin— A layer of insulation that surrounds the nerve fibers in the brain and spinal cord.

Plaque— Patches of scar tissue that form where the layer of yelin covering the nerve fibers is destroyed by the multiple sclerosis disease process.

Primary progressive— A pattern of symptoms of multiple sclerosis in which the disease progresses without remission, or with occasional plateaus or slight improvements.

Relapsing-remitting— A pattern of symptoms of multiple sclerosis in which symptomatic attacks occur that last 24 hours or more, followed by complete or almost complete improvement.

Secondary progressive— A pattern of symptoms of multiple sclerosis in which there are relapses and remissions, followed by more steady progression of symptoms.

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Multiple Sclerosis

Multiple sclerosis

Definition

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system . The disease results in injury to the myelin sheath (the fatty matter that covers the axons of the nerve cells), the oligodendrocytes (the cells that produce myelin) and, to a lesser extent, the axons and nerve cells themselves. The symptoms of multiple sclerosis vary, depending in part on the location of plaques (areas of thick scar tissue) within the central nervous system. Common symptoms include weakness and fatigue , sensory disturbances in the limbs, bladder or bowel dysfunction, problems with sexual function, and ataxia (loss of coordination). Although the disease may not be cured or prevented at this time, treatments are available to reduce severity and delay progression.

Description

Multiple, or disseminated, sclerosis (MS) is a slowly progressive disease of the central nervous system (CNS), that comprises the brain and spinal cord. In 1868, French physician Jean-Martin Charcot (1825–1893) produced his lectures on "Sclerose en plaques," providing the first detailed clinical description of the disease. The cause of multiple sclerosis is unknown, and it cannot be prevented or cured. Great progress, however, is being made in treating and identifying underlying mechanisms that trigger the disease. The primary characteristic of MS is the destruction of myelin, a fatty insulation covering the nerve fibers. The end results of this process, called demyelination, are multiple patches of hard, scarred tissue called plaques. Another important feature in the disease is destruction of axons, the long filaments that carry electric impulses away from a nerve cell, which is now considered to be a major factor in the permanent disability that occurs with MS.

Multiple sclerosis is usually characterized by a relapsing remitting course in the early stages, with full or nearly full recovery initially. In the early stages, there may be little damage to axons. Over time, the disease enters an irreversible progressive phase of neurological deficit. Each relapse causes further loss of nervous tissue and progressive dysfunction. In some cases there may be chronic progression without remission or acute disease rapidly leading to death.

MS is a diverse disease. No two affected persons are the same and each will experience different combinations of symptoms with differing severity. The most common form is relapsing-remitting multiple sclerosis (RRMS), which affects 80–85% of people with MS. These patients develop disease relapses, often without a specific trigger, but possibly associated with infections. Disease relapses can last between 24 hours and several months, and the person may, or may not, completely recover. The disease is stable between relapses, although affected persons can have residual symptoms and disability.

After several years, the majority (70%) of persons with MS will develop secondary progressive multiple sclerosis (SPMS), whereby they experience a progressive neurological deterioration. They may still suffer from superimposed relapses. A subcategory of RRMS patients (around 20%) has benign MS. These patients have rare and mild relapses and a long course of disease with minimal or no disability. If patients have a steady neurological decline from the onset, without relapses, they are described as having primary-progressive multiple sclerosis (PPMS). This comprises approximately 15–20% of people with the disease

A fourth, rare type of MS is progressive-relapsing multiple sclerosis (PRMS), which is considered a variant of PPMS with similar prognosis. In patients with PRMS, there is a gradual neurological decline from the beginning. It is similar to PPMS, but has superimposed, acute relapses.

Demographics

According to the National Multiple Sclerosis Society, approximately 400,000 Americans acknowledge having MS, and every week about 200 people are diagnosed. Worldwide, MS may affect 2.5 million individuals. The usual age of onset is within the third and fourth decades, although the disease can begin in childhood and also above the age of 60 years. Overall, MS occurs more frequently in women than in men, and the female-to-male ratio is approximately of 2:1. This female predominance is less defined in patients with PPMS, which typically develops at a later age.

There is a variation in the worldwide distribution of MS, with the highest prevalence in the northern and central Europe, northern North America and southeastern

Australia. Clusters, or areas with more than the expected amount, occur. There are also racial differences, with a low prevalence in Asians and Africans or people of African descent, and a higher frequency in Caucasians, especially of northern European descendent. MS is rare between the equator and latitudes 30°–35° north and south. The prevalence of MS increases proportionally with increased distance from the equator. There is no satisfactory explanation of this phenomenon, although certain variables have been researched. These include environmental factors, such as climate, humidity, hours of daily sunshine, resistance to certain viruses, and even consumption of cow's milk.

Causes and symptoms

The causes of multiple sclerosis remain unknown, but it is widely accepted that susceptibility to MS is determined by a complex interaction between susceptibility genes and environment. The most popular current theory is that the disease occurs in people with a genetic susceptibility, who are exposed to some environmental assault (a virus or a toxin) that disrupts the blood-brain barrier, a protective membrane that controls the passage of substances from the blood into the central nervous system. Most researchers consider MS to be an autoimmune disease-one in which the body, through its immune system, launches a defensive attack against its own tissues. Immune factors converge in the nerve cells and trigger inflammation and an autoimmune attack on myelin and axons. Still, a number of disease patterns have been observed in MS patients, and some experts believe that MS may prove to be not a single disorder, but may represent several diseases with different causes.

Components of myelin such as myelin basic protein have been the focus of much research because, when injected into laboratory animals, they can precipitate experimental allergic encephalomyelitis (EAE), a chronic relapsing brain and spinal cord disease that resembles MS. The injected myelin probably stimulates the immune system to produce anti-myelin T-cells that attack the animal's own myelin.

Increasing scientific evidence suggests that genetics may play a role in determining a person's susceptibility to MS. No specific gene has been identified and it seems to have a mode of inheritance that involves multiple genes. Twin studies have shown an increased risk of 30% in identical twins, and around 5% in fraternal twins. First-degree relatives of a person with MS have a two or three percent increased risk, which, although small, is higher than in the general population. Further indications that more than one gene is involved in MS susceptibility comes from studies of families in which more than one member has MS.

Several research teams found that people with MS inherit certain regions on individual genes more frequently than people without MS. Of particular interest is the human leukocyte antigen (HLA) or major histocompatibility complex region on chromosome 6. HLAs are genetically determined proteins that influence the immune system. Another interesting candidate is CD24, which has shown to be essential for the induction of EAE in mice. CD24 is a cell surface protein with expression in a variety of cell types that can participate in the rise of MS, including activated T-cells.

An infectious cause of MS has been indicated by some studies as well as by similarities to infectious demyelinating diseases. However, infectious agents more likely shape the immune response that may induce the disease under special circumstances. Evidence is mounting that infection with the Epstein-Barr virus (EBV), which can cause mononucleosis, may also increase the risk of developing multiple sclerosis later in life. Researchers have shown that people with multiple sclerosis tend to carry higher levels of antibodies to the Epstein-Barr virus and that they seem to be at higher risk for the disease. Some of the immune cells that become programmed to attack the Epstein-Barr virus may begin to attack myelin as well.

Environmental factors, other than infectious agents, for which there is some evidence of an association with MS, include toxins, low sunlight exposure, diet factors, and trauma.

Almost any neurological deficit can occur in MS, but there are several signs and symptoms that are characteristic and their presence should suggest MS as a possible diagnosis, particularly in a young adult.

Vision disorders such as optic neuritis can occur. Optic neuritis (ON) is an inflammation of the optic nerve characterized by acute or subacute loss of vision usually in one, but occasionally in both eyes. The visual loss evolves over a period of hours or days. Vision returns to normal within two months, but may deteriorate in later years. Previous history of optic neuritis in a person who develops a neurological illness will strongly support the diagnosis of MS.

Cognitive (thought) impairment is thought to affect 40–70% of MS patients and can be present even in the early stages of MS. Approximately one-third of people with MS have some degree of memory loss. Other areas of cognitive function particularly affected in the MS patient include sustained attention, verbal fluency, and spatial perception. Dementia (loss of intellectual function) is often common in the latter stages of MS.

Many MS patients are temperature sensitive. In hotter weather or during a period of raised body temperature, their MS symptoms worsen. Most frequently, vision is affected and muscle weakness occurs.

About two-thirds of MS patients experience pain at some point during the course of the disease and 40% are never pain free. MS causes many pain syndromes; some are acute, while others are chronic. Some worsen with age and disease progression. Pain syndromes associated with MS are trigeminal (facial) pain, powerful spasms and cramps, optic neuritis pain, pressure pain, stiffened joints, and a variety of sensations including feelings of itching, burning, and shooting pain.

The Lhermitte's sign can occur, which is actually more of a symptom than a sign. A tingling or electric-like sensation down the back and legs is felt upon flexing the neck. The symptom is non-specific, but occurs more frequently in MS than in any other condition and provides an important clue to the correct diagnosis.

Urinary incontinence affects up to 90% of people with multiple sclerosis and usually occurs before major physical disability is apparent. Bladder problems are due to plaques in the spinal cord. If demyelination occurs in both controlling pathways, the bladder will neither store urine nor empty it properly. Constipation affects about 40% of people with MS. Bowel incontinence and urgency of defecation can also occur in about half of people with MS.

Fatigue is a common complaint in MS. Characteristics of fatigue include muscle weakness, coordination problems, ataxia, transient deafness, changes in taste or smell and numbness of the extremities. Spasticity occurs in up to 90% of MS patients and it can be painful and distressing. Spasticity is characterized by weakness, loss of dexterity, and the inability to control specific movements. It is usually more severe in the legs and torso.

Sexual dysfunction is common among people with multiple sclerosis. If MS damages the nerve pathways from the brain to the sexual organs via the spinal cord, sexual response can be directly affected. Physicians and people with MS often neglect to deal with this aspect of the disease, and both treatments and strategies for success are available.

Depression is common in MS; some studies show that over 50% of people with MS have depression at some point in their lifetime. There is also an increased risk of suicide. If depression is present, it should be treated prior to initiating MS therapy. Depression in those with MS is treated in the same way as the general population.

Diagnosis

MS diagnosis is based upon an individual's history of clinical symptoms and neurological examination. A qualified physician, often a neurologist , must thoroughly review all symptoms experienced by an individual to suspect MS. Other conditions with similar symptoms must be ruled out, often requiring various tests.

The diagnosis of MS is usually made in a young adult with relapsing and remitting symptoms referable to different areas of CNS white matter. Diagnosis is more difficult in a patient with the recent onset of neurological complaints or with a primary progressive clinical course.

Laboratory studies include blood work to exclude collagen vascular disease, infections (ie, Lyme disease , syphilis), endocrine abnormalities, vitamin B-12 deficiency, sarcoidosis, and vasculitis . The examination of cerebrospinal fluid (CSF) has been used to support the diagnosis of MS. The presence of myelin basic protein in the CSF of an MS patient may be highly suggestive of activity of the MS process, but its absence does not rule out active disease.

A newer neuroimaging technique, magnetic resonance spectroscopy (MRS), has been useful in following NAA (N-acetyl-aspartate) levels in patients with multiple sclerosis. NAA is an amino acid found in neurons and axons of the mature brain. In patients with relapsing-remitting MS, NAA levels are reduced, suggesting axonal loss; however, in patients with secondary progressive MS with more disability, the NAA levels are reduced more significantly. In fact, patients with MS had lower levels of NAA even in areas of the brain previously thought to be unaffected, when compared with levels in normal persons.

Magnetic resonance imaging (MRI) remains the imaging procedure of choice for diagnosing and monitoring disease progression in the brain and spinal cord. This test can show brain abnormalities in 90–95% of patients and spinal cord lesions in up to 75% of cases, especially in elderly patients. However, MRI alone cannot be used to diagnose MS. Evoked potential tests that measure how quickly and accurately a person's nervous system responds to certain stimulation have been the most useful neurophysiological studies for evaluation of MS.

At the onset, MS may be mistaken for other inflammatory diseases of the central nervous system, such as Behçet disease, antiphospholipid syndrome or acute disseminated encephalomyelitis (ADEM). Pseudotumoral MS may be reminiscent of lymphoma, other tumors (glial tumors), or infectious diseases (like Lyme disease, HTLV1 infection or abcess). Recurrent relapses of neurological impairment may also be mistaken for cavernomatosis. In most cases, MRI findings, cerebrospinal fluid analysis, evoked potentials, the association with systemic signs and the relapsing remitting nature of the disease allow physicians to exclude other diseases, and to arrive at a diagnosis of MS.

Treatment team

The multidisciplinary team usually includes specialists in neurology, urology, ophthalmology, neuropsychology, and social work.

Treatment

The three goals of drug therapy in the treatment of MS are management of acute episodes, prevention of disease progression, and treatment of chronic symptoms. Specific symptoms that may be treated include muscle spasticity, lack of co-ordination, tremor, fatigue, pain, bladder and bowel dysfunctions, sexual dysfunction and depression.

Exacerbations (episodes of worsening symptoms) can be defined as temporary flare-ups, sometimes referred to as attacks or relapses. Most relapses show a degree of spontaneous recovery, but treatment is offered for those relapses that have a severe impact on function. Steroids are the treatment of choice for relapses, usually methyl-prednisolone given orally or by intravenous infusion. Before starting steroids, infection should be excluded because steroids have immunosuppressant action and can exacerbate the infection.

Disease modifying treatments are aimed at slowing disease progression. The two current types of immunomodulatory agents used as a first line treatment are interferon beta and glatiramer acetate. Interferon beta has proved effective with RRMS and SPMS. There is currently no evidence for improvement with PPMS. Discontinuation of the treatment may be necessary because of intolerance to side effects, when a pregnancy is planned, or when it is no longer effective. Glatiramer is the appropriate treatment to reduce relapse frequency in patients with RRMS and it should not be used for both PPMS and SPMS. Stopping criteria for glatiramer are the same of interferon beta.

A number of treatments are available for managing MS chronic symptoms and complications, each one with specific drugs. Indeed, symptomatic treatment, along with supportive measures and rehabilitation, are a major part of the MS treatment.

Recovery and rehabilitation

When recovering from a symptom flare-up or learning to cope with a change in mobility, rehabilitation through physical therapy can be of great value training patients to improve mobility and to decrease spasticity and strengthen muscles. Some of those who have a physically demanding or highly stressful job may choose to make a career change, in which case vocational training is helpful.

Occupational therapy helps in assessing the patient's functional abilities in completing activities of daily living, assessing fine motor skills, and evaluating for adaptive equipment and assistive technology needs. Speech therapists assess the patient's speech, language, and swallowing and may work with the patient on compensatory techniques to manage cognitive problems.

Clinical trials

The National Institute of Neurological Disorders and Stroke (NINDS) is recruiting patients to evaluate the safety, tolerability, and effect of the drug Rolipram on MS. The NINDS is also recruiting patients with relapsing-remitting or secondary progressive multiple sclerosis to examine the safety and effectiveness of Zenapax (a laboratory-manufactured antibody) in treatment of MS. More information is available at the website: <http://www.clinicaltrials.gov>, a clinical trial service sponsored by the United States government.

Prognosis

It is generally very difficult to predict the course of MS. The disorder varies greatly in each individual, but most people with MS can expect to live 95% of the normal life expectancy. Some studies have shown that people who have few attacks in the first several years after diagnosis, long intervals between attacks, complete recovery from attacks, and attacks that are sensory in nature (i.e., numbness or tingling) tend to fare better. People who have early symptoms of tremor, difficulty in walking, or who have frequent attacks with incomplete recoveries, or more lesions visible on MRI scans early on, tend to have a more progressive disease course.

Special concerns

People with should avoid caffeine-containing beverage, which can actually be dehydrating. The diet should also be rich in fiber, particularly from whole grains, fruits and vegetables to increase digestive motility and reduce constipation. Maintenance of weight in the normal range is also desirable in order to diminishes stress on the joints and skeletal muscles.

Gait difficulty (difficulty with walking) may worsen during pregnancy, and assistive devices for walking or a wheelchair are useful at this time. During pregnancy, bladder and bowel problems may also be aggravated in women with MS who already have these dysfunctions.

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Multiple Sclerosis

Multiple sclerosis

Definition

Multiple sclerosis is a chronic, degenerative disease of the central nervous system (CNS). The CNS is comprised of the brain and the spinal cord. In the CNS, the nerves are covered by a protective layer called the myelin sheath. Myelin helps keep the nerve healthy. It also improves nerve conduction. In multiple sclerosis, inflammation causes the nerves to gradually lose this myelin cover. This repeated inflammation and erosion leads to scarring (sclerosis), which impairs the nerve's ability to conduct impulses. Eventually, even the nerves themselves are affected. Because the nervous system controls and coordinates a number of body functions, patients with MS gradually lose a variety of functions, including memory and the ability to see, speak or walk.

Description

Multiple sclerosis is a chronic debilitating disease that affects as many at 350,000 in the United States alone (2.5 million worldwide). Most patients are first diagnosed of the disease at age 20-40. However, the disease may appear as early as age 12 or as late as age 50. MS strikes women earlier in life. Women are also affected more frequently than men and whites more often than other races.

Causes & symptoms

The causes of multiple sclerosis are still unknown, although many factorsare suspected. In the United States, whites are diagnosed with MS twice as often as blacks or Hispanics. Asians are the least affected. There is some consensus, however, that the following factors may contribute to the development of multiple sclerosis:

Genetic heredity. Family members of multiple sclerosis patients have a 1 in 50 chance of having MS; the odds for people without an affected family member are 1 in 1,000. If an identical twin is diagnosed with MS, the remaining twin has a 1 in 3 chance of becoming affected as well. Recent research has shown that several autoimmune diseases, including MS, share a common genetic link. In other words, patients with MS might share common genes with family members that have other autoimmune diseases like systemic lupus, rheumatoid arthritis , and others.

Viral infection. Most MS patients have high levels of antibodies to measles and other viruses. Therefore, multiple sclerosis may be the body's delayed immune reaction to viruses such as measles, Herpes simplex, rubella , and parainfluenza. A 2001 study also suggested that Epstein-Barr virus, the virus that causes mononucleosis , probably increases risk of MS.

Autoimmune reaction. Scientists know that MS is an autoimmune disorder, an illness in which the body attacks its own myelin as if it were a foreign substance. Although research has identified which immune cells are responsible and how they are activated, no one knows what causes the immune system to begin this attack.

Geography. Countries in the temperate zones (above 40°) such as Northern Europe, North America, Australia, and New Zealand have significantly higher incidence of multiple sclerosis than countries in the tropics. In the United States, people who live below the 37th parallel develop MS at a rate of 57–78 cases per 100,000 people. Those who live above the line have a prevalence rate of 110–140 cases per 100,000 people.

Diet. Studies have shown that populations at high risk of developing multiple sclerosis tend to consume a lot of dairy products and animal fats. On the contrary, in countries such as Japan, people eat few dairy products but consume lots of fish, soy-rich foods, and seeds, which are good sources of essential fatty acids . The incidence rates in these countries are very low. Thus, essential fatty acid deficiency due to excessive consumption of saturated fats may contribute to the development of multiple sclerosis.

Diagnosis

In order to determine whether or not a patient has multiple sclerosis, doctors often rely on the Schumacher criteria:

Patient's symptoms indicate neurological damage in more than one areas.

Patient's symptoms have worsened for more than six months.

There are at least two events (each lasting for more than one day) separated by at least one month.

Patient does not have stroke , lupus, or any disease that may have similar symptoms.

A diagnosis of multiple sclerosis is made when patient's symptoms fit Schumacher's criteria and neurological exams, MRI, and laboratory results also show corresponding abnormalities. In 2001, a panel convened by the National Multiple Sclerosis Society wrote new diagnostic criteria for MS, the first update in about 20 years. The new criteria formally recommend MRI and outline how doctors should use the results of tests like cerebral spinal fluid analysis.

MS symptoms vary significantly in terms of severity, intensity and duration. Sensory symptoms are the first warning signs. Many patients notice color distortion, blurred or double vision, and temporary blindness. Their senses of smell, hearing, touch, and taste are also affected. They experience muscle weakness and difficulty walking, as well as muscle spasms and numbness, tingling, or prickling ("pins and needles") sensations called paresthesias. As the disease progresses, sudden partial or complete paralysis of the arms or legs is common, as are an inability to speak clearly, move without tremors , or hear clearly. Mental functions are also affected. Patients can not concentrate or remember as clearly as before. They often become depressed. They may laugh or cry uncontrollably. As conditions worsen, they lose control of bodily functions. Some patients find that hot weather exacerbates their symptoms. Cold baths or air conditioning may help during these periods. There are also periods, called remissions, in which patients are free of symptoms; remission can be complete or partial.

While there is a rare, rapidly progressing form of MS that can be fatal in as little as a few days or weeks, MS generally affects the quality of life more than it diminishes life expectancy. Most patients can look forward to decades of life after diagnosis. Many are able to continue to live a relatively normal life for at least 20 years after onset, although some patients become disabled within a few months of being diagnosed. In addition, because MS patients are frequently forced into immobility

SYMPTOMS OF MULTIPLE SCLEROSIS

Symptoms

Numbness in one or more limbs

Tingling in one or more limbs and chest

Tremors

Lack of muscular coordination

Blurred vision

Incontinence

Exhaustion and weakness in limbs

and spend a lot of time sitting in wheelchairs they are susceptible to such common complications of the disabled as urinary tract infections , skin ulcers, pneumonia , or pulmonary embolism (blood clot in the lung) in addition to side effects from prescribed drugs.

Treatment

Nutritional therapy

Many multiple sclerosis patients follow a low-fat diet developed by Dr. Roy Swank, who recommends his diet to slow down disease progression. The following are his recommendations:

Consume no more than 10 g of saturated fat per day.

Limit polyunsaturated fat consumption to 50 g or less per day.

Take 1 tbsp of cod liver oil per day to supplement essential fatty-acid intake. Cod liver oil is a good source of omega-3 fatty acid, one of the two essential fatty acids.

Consume adequate amount of protein in the diet, preferably plant protein such as soy, beans, seeds, and nuts.

Eat more fish, a good source of omega-3 fatty acid. Swank recommends having fish three or more times per week. Omega-3 fatty acid is believed to support myelin production and improve nerve function.

In addition to following the Swank diet, Dr. Michael Murray and Dr. Joseph Pizzorno, the authors of the book Encyclopedia of Natural Medicine also recommend the following nutritional supplements:

Flaxseed oil. Murray and Pizzorno recommend replacing the fish oil in Swank's diet with flaxseed oil because the latter can provide both omega-3 and omega-6 fatty acids . Omega-6 fats, studies have shown, also help alleviate MS symptoms.

Antioxidants such as selenium, vitamin C , and vitamin E . Patients with multiple sclerosis often have antioxidant deficiency.

Vitamin B12. MS patients often lack Vitamin B12 , and correcting this deficiency is believed to help decrease myelin destruction.

Exercise and physical therapy

Almost any form of exercise or movement therapy is beneficial for MS patients. For patients too weak to exercise alone, a massage or assisted physical therapy should be helpful to improve circulation to the limbs and promote well-being. Those that are less restricted may find t'ai chi, qigong, yoga, martial arts , conventional cardiovascular exercise, and/or water aerobics helpful.

Other treatments

Other alternative treatments such as aromatherapy (body massage with rosemary or juniper essential oils ) and hydrotherapy (hot or cold baths used to treat affected areas, also a program of exercise performed in water) may also improve muscle strength in MS patients. Chinese herbs, especially ginseng, are also helpful in managing the disease. Wearing a cooling vest may also help, according to a 2001 study. The vest cools patients (without affecting their temperatures) and also appears to promote production of white cell nitrous oxide, which may play a role in MS.

Allopathic treatment

Standard treatment consists of an exercise program, diet modification, and medication. Three relatively new drugs may be prescribed: beta-interferon A (Avonex), which can limit the progressions of disability; beta-interferon-B (Betaseron), which reduces the number and severity of relapses; and Glatiramer acetate (Copaxone), which helps prevent relapse in patients with the relapsing-remitting (RR) type of MS. (These are patients who have a period of time with no or few symptoms [remission] following acute exacerbations [relapse] of disease.) All are administered by injection. These drugs have significant side effects including fever , tiredness, weakness, chills , muscle aches and inflammation at injection sites. Avonex may be better tolerated than Betaseron.

For symptomatic treatment of muscle spasm, Baclofen is most effective; its dosage must be carefully tailored to specific patient's needs. An implantable infusion pump that delivers the drug directly into the spinal cord can be used for patients with severe spasticity. Diazepam (valium) is sometimes given together with baclofen to increase its effectiveness. Alternative antispastic drugs are tizanidine and dantrolene. Steroids such as methylprednisolone and prednisone are also sometimes used to treat flare-ups.

Expected results

Patients whose symptoms worsen quickly right after diagnosis, those who have significant impairment in muscle movement or brain functions at onset and who have very abnormal magnetic resonance imaging (MRI) results at the beginning have poor prognosis. On the other hand, patients who recover quickly after the initial symptoms or those who experience only sensory impairment for five years or more after diagnosis often are able to maintain work longer and live longer than those with chronic progressive multiple sclerosis.

Prevention

There is no way to prevent the onset of multiple sclerosis, though a diet low in saturated fat may be helpful.

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Multiple Sclerosis

Encyclopedia of Public Health
COPYRIGHT 2002 The Gale Group Inc.

MULTIPLE SCLEROSIS

Multiple sclerosis (MS) is a disorder that affects primarily the myelinated white matter of the central nervous system (CNS), the brain, optic nerves, and spinal cord. There is no known cause. Myelin is the fatty sheath that insulates nerve fibers (axons). Partial or complete loss of myelin due to MS impairs nerve conduction through affected axons, producing symptoms and functional impairment referable to them. Thus, MS may produce mild to severe weakness, lack of coordination, disordered sensations, partial loss of vision, impaired control of bladder and bowel function, impaired cognition, or any combination of these effects.

Early in the course of the disorder, symptoms are often brief and transient—impaired function caused by a particular episode, or relapse, tends to improve, in what is called a "remission." Remissions may be partial or total. However, over the course of years, incomplete recovery from relapses may occur, leading to the accumulation of impaired function and producing some degree of disability in about 70 percent of affected individuals. Among those who become disabled, some do not experience improvement from the beginning. However, it is important to realize that, although it is a common cause of disability among young to middle-aged individuals, MS is very unpredictable in a particular person; it does not necessarily disable and it does not necessarily shorten life span appreciably.

The average age of occurrence of the first symptom(s) is thirty-three, but MS may show itself as early as childhood or as late as age sixty or beyond. It affects almost twice as many women as men, and primarily in men and women of predominantly or mixed Caucasian parentage. Approximately 350,000 people in the United States have MS, and it is estimated to affect about 3 million people worldwide. However, MS is rare among South and East Asians, and among blacks in Africa. These differences suggest that susceptibility to develop MS may be genetically determined. However, among identical twins where one has MS, no more than 50 percent of the unaffected twins will go on to develop MS. This lends support to the concept that an environmental trigger, perhaps a viral infection, acts in concert with the genetic setting to produce MS. Siblings and children of those with MS have a somewhat greater chance of developing MS, but no specific genetic pattern has been identified. It is likely that multiple genes are involved in conferring susceptibility.

The frequency of MS has been studied closely since the 1930s. However, despite improved diagnostic methods (and improved treatment), the incidence (number of new cases per year in the population) does not appear to have increased.

Even after many years of intensive research, the cause of MS remains elusive, and it is a challenging subject for research. The most widely accepted hypothesis at this time is that an infection triggers an autoimmune response in genetically susceptible individuals. Autoimmunity implies that the body's immune-defense system erroneously and inappropriately attacks normal tissues, in this case the myelin and/or the cell that synthesizes and supports myelin, the oligodendrocyte.

Diagnosing MS is often very challenging. To do so involves documenting the occurrence of two or more episodes of impaired function, occurring at different times, that are referable to CNS white matter, while excluding all other possible causes of the problems. The fact that MS affects primarily the CNS white matter makes it possible to visualize very accurately areas of inflammation and demyelination via magnetic resonance imaging (MRI). MRI is an invaluable aid to diagnosis, although the MRI picture alone is not sufficient to be certain of the diagnosis. MRI is also used to identify new relapses, and to quantify the number and size of past episodes. Similarly, the cerebrospinal fluid typically shows alterations that may support a diagnosis, but a diagnosis cannot be made without appropriate clinical history and neurological examination.

Even though its cause is still mysterious, treatments have been developed that have reduced the number of relapses by more than 30 percent. These agents include recombinant interferon beta (IFNß; particular brand names include Avonex, Betaseron, and Rebif) and glatiramer acetate (Copaxone), each of which is widely used. Laboratory and clinical studies of many other possible treatments are underway, which is a very hopeful indicator of more effective therapies to come in the future. In addition to these disease-modifying agents, treatment often includes the use of medications intended for purely symptomatic relief, as well as physical therapy and occupational therapy. The challenges posed by an uncertain clinical course, and by chronic disability among some individuals, makes psychological support a key part of management.

The National Multiple Sclerosis Society (http://nmss.org/), similar organizations in other countries, and the International Federation of Multiple Sclerosis Societies (http://www.who.int/ina-ngo/ngo/ngo076.htm) are excellent sources of further information about the disorder, ongoing research, and treatment.

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multiple sclerosis

The Columbia Encyclopedia, 6th ed.

Copyright The Columbia University Press

multiple sclerosis (MS), chronic, slowly progressive autoimmune disease in which the body's immune system attacks the protective myelin sheaths that surround the nerve cells of the brain and spinal cord (a process called demyelination), resulting in damaged areas that are unable to transmit nerve impulses. The disease also gradually damages the nerves themselves. There are elevated numbers of lymphocytes in the cerebral spinal fluid and of T cells in the blood (see immunity).

The onset of MS is usually at age 20 to 40 years, and its many symptoms affect almost every system of the body. There may be visual difficulties, emotional disturbances, speech disorders, convulsions, paralysis or numbness of various regions of the body, bladder disturbances, and muscular weakness. The course of the disease varies greatly from person to person. In some patients, the symptoms remit and return, sometimes at frequent intervals and sometimes after several years. In others the disease progresses steadily.

There is a genetic predisposition to MS, and environmental factors also seem to play some role. The disease is more common in temperate climates (1:2,000) than in the tropics (1:10,000).

There is no cure for MS, but a number of drugs—the first of which became available in the 1990s—can slow its underlying progress and/or reduce the frequency of attacks. These are beta interferon (a synthetic version of a natural substance produced by the immune system), glatiramer acetate, and natalizumab.

See R. Rubinstein, Take It Or Leave It: Aspects of Being Ill (1989); U.S. Dept. of Health and Human Services, Warren Grant Magnuson Clinical Center, Multiple Sclerosis (1990).

Cite this article Pick a style below, and copy the text for your bibliography.

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Multiple Sclerosis

UXL Complete Health Resource
COPYRIGHT 2001 The Gale Group, Inc.

MULTIPLE SCLEROSIS

DEFINITION

Multiple sclerosis (MS; pronounced multiple skluh-RO-siss) is a chronic autoimmune disorder (see autoimmune disorders entry) that affects the nerves. "Chronic" means that it develops slowly over time; "autoimmune" means that the body's immune system becomes confused about some part of the body it is designed to protect. It attacks that part of the body as if it were a foreign invader. MS affects a person's ability to move, to feel, and to control his or her body functions.

DESCRIPTION

Nerve messages consist of electrical impulses that travel through the body by means of nerve cells. Nerve cells are also called neurons. Neurons are covered by a thin layer of tissue known as myelin (pronounced MY-uh-lin) that acts as an insulator. It prevents the electrical currents that pass through neurons from leaking away.

MS occurs when the myelin that surrounds neurons in the brain and spinal cord is destroyed. The loss of myelin causes electrical impulses to pass through neurons more slowly. Over time, scar tissue forms around the damaged myelin. This scar tissue, called plaque (pronounced PLAK), also reduces the neurons' ability to function normally.

Damage to myelin can cause a variety of symptoms. A person may lose the ability to use his or her senses, such as touch and vision. Loss of muscular control also occurs because movement of muscles is controlled by nerves. A person with MS may have problems with balance, strength, and coordination.

MS affects more than 250,000 people in the United States. Most people experience their first symptoms between the ages of twenty and forty. Symptoms rarely begin before the age of fifteen or after sixty. Women are twice as likely to get MS as men, especially in their early years. MS is more common among some ethnic groups than others. For example, the disease is more common in North America and northern Europe than in other parts of the world. MS is very rare among Asians, Indians of North and South America, and Eskimos.

Multiple Sclerosis: Words to Know

Evoked potential test (EPT):

A test that measures the brain's electrical response to certain kinds of stimulation, such as light in the eyes, sound in the ears, or touch on the skin.

Myelin:

A layer of tissue that surrounds nerves and acts as an insulator.

Plaque:

Patches of scar tissue that form in areas where myelin tissue has been destroyed.

Primary progressive:

A form of multiple sclerosis in which the disease continually becomes worse without any major improvement.

Relapsing-remitting:

A form of multiple sclerosis in which symptoms appear for at least twenty-four hours and then disappear for a period of time.

Secondary progressive:

A form of multiple sclerosis in which a period of relapses and remissions is followed by another period in which the disease becomes progressively worse without improvement.

CAUSES

Multiple sclerosis is an autoimmune disease in which the immune system begins to attack myelin. It "decides" that the myelin is a foreign substance that threatens the body and must be destroyed. Researchers do not know why this happens.

As myelin is destroyed, neurons no longer function normally. Brain neurons cannot receive and process information from the outside world. Neurons in the brain and the spinal cord cannot send messages to other parts of the body. Normal muscular functions, such as standing, walking, lifting, and turning, become difficult or impossible.

The progress of MS seems to depend on the appearance of new plaques. These plaques slow down nerve messages and worsen the symptoms of the disease. Scientists do not understand how, where, and why plaques develop. For that reason, they cannot predict how the disease will progress in any one person over time.

Finding the reason for a body's autoimmune reaction to myelin is a major field of research. So far, no final answer has been found. Some possible factors leading to this condition are a person's heredity (his or her genes), environmental factors, viruses, or a combination of these factors.

The reason that heredity is considered a possible factor is that MS seems to run in some families. A person who has a family member with MS is more likely to develop the disease than someone whose family has no history of MS. In addition, the tendency of some ethnic groups to contract (get) the disease suggests a hereditary factor.

Support for environmental factors comes from data on migration. Migration is the process of moving from one part of the world to another part. Studies have been done on people who move from a low-risk part of the world (such as Asia) to a high-risk part (such as the United States). Young people who make such moves have a higher risk of developing MS than those of the same age who remained at home. Older people do not experience an increased risk. These data suggest that environmental conditions in the new location might be responsible for MS.

One possible environmental factor is viruses. There are some kinds of viruses that attack the body very slowly. HIV, the virus that causes AIDS (see AIDS entry), is one such virus. Some researchers think that a slow-acting virus may be responsible for MS. But no data supporting this theory have yet been produced.

SYMPTOMS

Multiple sclerosis can develop in one of three patterns. The most common pattern is called "relapsing-remitting." In this pattern, symptoms appear and then disappear. A person may feel fine for a while and then experience the symptoms of MS for a period of twenty-four hours or more. Then the symptoms disappear again for a span of time. That span may be as long as a year or more at the beginning of the disease. But the span grows shorter as the person becomes older. This pattern is especially common in younger people with MS.

"Primary progressive" is a second pattern. In this pattern, the disease simply gets worse over time. A person may have brief periods when the disease does not get worse, but these are rare. The primary progressive pattern is more common in older people.

The "secondary progressive" pattern is a combination of the first two patterns. A patient first goes through a period of relapsing and remitting. Eventually, however, the disease just continues to get worse, as in the primary progressive pattern.

Between 10 percent and 20 percent of MS patients have a benign form of MS. Benign means that the symptoms do not change very much throughout a person's life.

The actual symptoms of MS vary considerably from person to person. The reason for this is that plaques form in different places and at different times in different individuals. Some initial symptoms of the disease include:

Muscle weakness, causing difficulty in walking

Loss of coordination or balance

Numbness, feelings of "pins and needles," or other abnormal sensations

Problems with vision, including blurred or double vision

As the disease develops, other symptoms may appear. These include:

Fatigue

Muscle stiffness

Tremors (shaking)

Paralysis

Pain

Vertigo (dizziness, light-headedness)

Difficulty with speech and/or swallowing

Loss of bowel or bladder control

Constipation

Sexual problems

Changes in one's ability to think clearly

Weakness in one or both legs is common. It is often the first symptom noticed by a person with MS. Excessive tightness of muscles is also common. It may actually cause more problems than muscular weakness.

Damage to myelin in the optical (eye) nerves can cause visual problems, such as blurred vision, changes in color vision, and even blindness. The condition may affect one or both eyes.

More than half of all people with MS have pain during the course of their disease. Many experience pain nearly all the time, often because of muscle spasticity (stiffness). The pain is often a sharp, stabbing pain, especially in the face, neck, or back. Numbness and weakness in the face are also common.

Some mental changes that can occur include loss of memory, depression, and personality changes. Some of these changes may result from damage to neurons. Others may be a side effect caused by the patient's despair about the disease. In less common cases, a person with MS may actually feel happier than usual.

The symptoms of MS can be affected by environmental conditions. Heat; increased body temperature; vigorous physical activity; or exposure to sun, hot baths, or showers can make symptoms worse.

DIAGNOSIS

Sometimes a doctor can make a reliable diagnosis of MS fairly easily and quickly. The distribution of symptoms is important since MS affects many different areas of the body over a period of time. The pattern of symptoms is also important. A case of relapsing-remitting MS can often be diagnosed because of the way the symptoms come and go.

Since the symptoms of MS are similar to those of other diseases, diagnosis can often be difficult and complicated. Many tests and extended observation may be necessary to decide what is causing the patient's symptoms.

The usual medical procedures used to make a diagnosis include a medical history, a standard neurological (nervous system) examination, and several laboratory tests. Among the tests most commonly used to confirm or rule out a diagnosis of MS are:

Magnetic resonance imaging (MRI) can show plaques on the brain and spinal cord. But plaques are present with other disorders as well. For example, the plaques caused by MS are sometimes difficult to distinguish from those caused by strokes (see stroke entry) or the simple process of aging.

A lumbar puncture (spinal tap) is a process in which cerebrospinal fluid (CSF) is removed from the patient's spine with a long, thin needle. The CSF is then studied. The presence of white blood cells and other substances may be a clue to the presence of MS.

Evoked potential tests (EPT) are tests that measure how quickly an electrical current passes through neurons. Scientists know the normal rate at which currents pass. If they move more slowly than normal, plaques may be present. An EPT can be conducted in various ways. One method is to apply a small electrical charge to the skin. A light can also be shined into a person's eyes. Or a tone can be sounded near his or her ears.

The neurologist (nerve specialist) conducting these tests may decide the patient is in one of three categories: "definite MS," "probable MS," or "possible MS." These three categories represent decreasing confidence in the accuracy of the diagnosis.

TREATMENT

Treatment of MS takes two forms. First, although there are no drugs that will actually cure the disease, there are drugs that can slow down the course of MS. Second, a variety of treatments can be used to ease the symptoms of multiple sclerosis.

As of 1997, three drugs had been approved for use with multiple sclerosis: Avonex, Betaseron, and Copaxone. All three reduce the rate of relapses in the relapsing-remitting form of MS. Each has other benefits as well. Avonex may slow the progress of physical damage; Betaseron may reduce the severity of symptoms; and Copaxone may decrease disability. All three drugs are administered by injection.

Immunosuppressant drugs have also been used to treat severe relapses. These drugs act on the immune system directly, causing it to work less effectively. The drugs carry some risks, so a patient may have to be hospitalized during treatment.

MS causes a large variety of symptoms. For that reason, many different treatments may be necessary to relieve those symptoms. A person should be vaccinated against influenza (see influenza entry). The vaccination can help protect against respiratory (breathing) problems, thus reducing the symptoms of MS. Preventing complications from MS is also important. Such complications include pneumonia (see pneumonia entry), bed sores, injuries from falls, or urinary infections. These complications lead to death more often than does MS.

Physical therapy is important in treating MS. It helps the patient strengthen and retrain affected muscles, maintain range of motion to prevent muscle stiffening, learn to use assistive devices such as canes and walkers, and learn safer and more energy-efficient ways of moving and sitting.

A program of physical therapy usually includes exercise and stretching. These activities can be taught and practiced at home. Swimming is often recommended. It provides a way for a patient to get exercise without becoming overheated.

Treatment programs usually include occupational therapy as well. People with MS are taught how to deal with daily activities, such as dressing, feeding, and washing. The occupational therapist can make suggestions for arranging the home and work environment so that an MS patient can function more safely and efficiently.

An MS patient may need training in bowel and bladder control. Drugs are sometimes used to deal with these problems. They help the patient to empty his or her bowel and bladder on a more normal schedule.

Spasticity can be treated with drugs as well. Baclofen (pronounced BAK-lo-fen) and diazepam (pronounced di-AZE-uh-pam, trade name Valium) are given by mouth, while botulin toxin (Botox) is given by injection. These drugs can help relieve the pain caused by spasticity. Back pain can be treated with over-the-counter pain relievers, such as aspirin or acetaminophen (pronounced uh-see-tuh-MIN-uh-fuhn, trade name Tylenol), or with physical therapy.

Fatigue can be treated by having the patient plan and follow a regular daily routine. The routine should allow for frequent rest periods. Drugs such as amantadine (pronounced uh-MANT-uh-deen, trade name Symmetrel) and pemoline (pronounced PEM-uh-leen, trade name Cylert) can help improve alertness and lessen fatigue. Corticosteroids are used to treat visual problems. Other types of drugs can be used to treat seizures, vertigo, and tremor.

Alternative Treatment

A variety of alternative treatments have been recommended for multiple sclerosis. So far, there are few scientific data to support most of these claims. For example, bee venom has been suggested as a treatment for MS. But studies have not supported this claim. Marijuana has been recommended for the relief of certain symptoms of MS, including tremor, pain, and spasticity. But the drug has side effects of its own. It is not widely recommended in the United States for the treatment of MS.

Some practitioners suggest that high doses of vitamins, minerals, and other dietary supplements can help slow the progress of MS. Specific nutrients recommended include linoleic (pronounced lin-uh-LEE-ik) acids, selenium, vitamin E, and a diet low in saturated fats.

PROGNOSIS

The prognosis for MS differs markedly from person to person. Most people with the disease can continue walking and functioning at home and work for many years after their diagnosis. Some conditions that favor a promising diagnosis include being female, having the relapsing-remitting form of the disease, having the first symptoms at an early age, having long periods of remission between relapses, and having vision and touch symptoms rather than muscular problems.

Less than 5 percent of people with MS have a severe progressive form of the disease that leads to death within five years. At the other extreme, 10 percent to 20 percent have a benign (relatively harmless) form with very slow or no progression of symptoms. On average, MS shortens the lives of women with the disease by about six years and men by about eleven years. Suicide is a significant cause of death in people with MS, especially among younger patients.

Most people experience the severest disabilities of MS within five years of diagnosis. After that point, disabilities do not continue to worsen significantly. If no disabilities appear within the first five years, they are unlikely to occur at all.

PREVENTION

There is no known way to prevent multiple sclerosis. Until the cause of the disease is discovered, that will continue to be the case. The symptoms of the disease can be reduced, however, by good nutrition; adequate rest; avoidance of stress, heat, and extreme physical exercise; and good bladder hygiene.

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multiple sclerosis

multiple sclerosis (MS, disseminated sclerosis) n. a chronic disease of the nervous system affecting young and middle-aged adults. The myelin sheaths surrounding nerves in the brain and spinal cord are damaged, which affects the function of the nerves involved. The course of the illness is usually characterized by recurrent relapses followed by remissions but a proportion of patients run a chronic progressive course. Symptoms include ataxia, abnormal eye movements (e.g. nystagmus), dysarthria, spastic weakness, and retrobulbar neuritis. www.mssociety.org.uk Website of the Multiple Sclerosis Society

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Multiple sclerosis (MS) is an inflammatory disease of the nervous system that disrupts communication between the brain and other parts of the body, resulting in episodes of weakness, paralysis, blindness, and other symptoms.

Jacqueline Du Pré was born in England in 1945. On her fifth birthday, her parents gave her a cello, and she started lessons the next year. At 16, Jacqueline made her debut in London and immediately became a household name. In 1967 she married the pianist and conductor Daniel Barenboim, and together the young, multitalented couple charmed the musical world. Six years later, Jacqueline could no longer feel the strings of her cello. By the mid-1970s, she was unable to dress herself or stand without help. In 1987, at the age of 42, she died of the disease called multiple sclerosis. Many people with MS are mildly affected, but in the most severe cases, like Jacqueline Du Prés, a person may be unable to write, speak, or walk.

Our bodies are able to act and react to the world around us thanks to a network of specialized tissue called the nervous system. This network is divided into two parts, called the central nervous system and the peripheral (pe-RIF-er-al) nervous system, which together process messages to and from all parts of the body. The basic unit of the nervous system is the nerve cell, or neuron, and humans have billions of them. Each neuron looks something like a kite. The top of the kite, or cell body, has many fingerlike extensions called dendrites that receive incoming messages. The tail of the kite, or axon, carries electrical messages from the cell over long distances. Dendrites and axons are called nerve fibers, and a nerve is a bundle of nerve fibers. Nerve cell fibers are wrapped (or sheathed) in a protective fatty substance called myelin (MY-a-lin).

The U.S. and the World

Worldwide, about 26,000 people died of multiple sclerosis in 1998 and about 1.5 million people have the disease.

As many as 350,000 Americans, or 1.2 percent of the population in 1999, have the disease, according to the Multiple Sclerosis Society. Many live 30 years or more with only mild symptoms. About 25 to 30 percent become disabled to the point where they need a wheelchair.

MS is an inflammation of the nerve fibers in the brain and spinal cord that results in scarred patches called plaques on the myelin sheath that protects the axons and dendrites. When plaques form, the signals passing through the cells may slow down or stop completely. Recent research suggests that, in addition to damaging myelin, MS sometimes slices through the nerve fiber; in other words, it destroys the neuron. About 1 million people worldwide have MS. The disease mostly strikes young adults between 20 and 40, and it affects about twice as many women as men. No one knows what causes MS, but it is believed to be an autoimmune disorder, that is, an attack by the body on its own cells.

When the Body Turns on Itself

A healthy body is continually primed to defend itself against disease-causing invaders such as bacteria, viruses, fungi, and parasites. The collection of techniques the body uses to resist disease is called the immune system. Usually the body is able to tell its own cells and foreign cells apart. But sometimes the mechanism for distinguishing self from non-self goes awry. In MS, the body no longer seems to recognize part of the myelin, and begins to attack it.

Are There Different Types of MS?

MS can follow several patterns. The most common type is called relapsing-remitting MS, in which symptoms come and go, sometimes with years in between when a person is perfectly fine. In about 50 percent of people with relapsing-remitting MS, the disease eventually will return for good, and when that happens, it is called secondary progressive MS. About 10 percent of people with MS have what is called primary progressive disease, which means that the disease does not go away after the first attack. Patients with primary progressive MS tend to be older (around 40 to 60 years old). A fourth and rare form of MS is called progressive-relapsing disease.

Whatever causes the immune system to react in the wrong way in MS is a mystery. Some scientists believe that a virus causes the immune system to attack the myelin sheaths. Others believe that factors in the environment (temperature, for instance) may trigger the disease. Genes* also may play a role in MS. Generally a person’s chances of getting MS are very low: less than a tenth of a percent. But if one person in a family has MS, then that person’s parents, children, and sisters and brothers have a higher risk of getting the disease. To complicate matters, it seems that more than one gene is involved in a person’s susceptibility to MS. In other words, many different factors are believed to be involved in MS. Research into how genes interact with one another and with the environment may help shed light on what causes MS.

are chemicals in the body that help determine a person’s characteristics, such as hair or eye color. They are inherited from a person’s parents and are contained in the chromosomes found in the cells of the body

MS may begin very dramatically, or the symptoms may be so mild that a person barely notices them. In the early stages of MS, people may find that simple motions like opening a window or climbing a few stairs tire their arms and legs. Feelings of numbness, or of “pins and needles,” are common. Patients often experience blurring and double vision. A person may become uncoordinated. In 70 percent of patients with MS, many of these early symptoms disappear, only to reappear months or years later. Over time, a person may become completely paralyzed. Many patients with MS have frustrating problems related to urination and bowel movements, such as incontinence (in-KON-ti-nens, the inability to control urination) and constipation. A person may become confused or forgetful owing to damage to the part of the brain that processes information. Some people with MS become depressed, or have fits of laughing or crying uncontrollably, for no reason.

It is not easy for a doctor to establish that a person has MS, because the symptoms are varied and not specific for the disease. Symptoms of MS can be confused with those that follow a viral infection or other diseases. A technique called magnetic resonance imaging, or MRI, is able to visualize the damage that MS causes in the brain. Another technique called magnetic resonance spectroscopy (spek-TROS-ko-pee) provides information about

The First Diagnosis of MS

Jean-Martin Charcot is known as the father of neurology, or the study of the nervous system. Charcot was born in Paris in 1825 and worked at the Salpêtrière Hospital his entire career. In 1868, a young woman came to his clinic with an unusual tremor and other neurological symptoms. The patient subsequently died, and in examining her brain, Charcot found the lesions* that we know today as the plaques caused by MS. Charcot treated patients with similar symptoms using electrical stimulation and strychnine (a nerve stimulant that also is used to poison rodents) in an effort to get the nerves working again. His treatments were unsuccessful, but in writing up the description of the disease and the changes in the brain it brings about, Charcot was the first to diagnose and to name MS. He laid the groundwork for future research, and his definition of the disease still holds today.

At present there is no cure for MS, and no way to prevent it. Some people do well with no treatment at all. Heat can make the symptoms of MS worse, and swimming or a cool bath may help. Until recently, people suffering severe relapses of MS were offered steroids (drugs with anti-inflammatory properties) as treatment. Steroids can reduce the duration and severity of attacks in some patients, but how they work is not known. Unfortunately, they also can cause acne, weight gain, psychosis, (losing touch with reality), and other serious side effects. These drugs are not recommended for long-term use.

Since 1993, three medications—Betaseron, Copaxone, and Avonex— have been available to treat relapsing-remitting MS. These medications are based on several different forms of a naturally occurring antiviral protein called beta interferon. Interferon reduces the number of MS attacks and may slow the disease down; they also appear to prevent new damage to myelin. A person receives interferon as an injection. Although interferon treatment has side effects, they are much milder than those of steroids, and include flulike symptoms, depression, and mild reactions at the place where the person receives the shot.

Scientists are working on many new therapies to treat MS. For example, immunotherapy aims to enhance the body’s own defense system to fight the disease. Because in MS the message, or electrical signal, that travels along a damaged nerve fiber is weak, researchers are studying ways of making the signals themselves stronger. Other research aims at finding ways of restoring the myelin sheath.

Most people with MS can expect to live at least 25 years following their diagnosis. One-third of people with MS will have very mild symptoms and be able to lead relatively normal lives. However, for people who become seriously disabled, life expectancy may be significantly reduced.

The diagnosis of MS is usually devastating because patients are often young adults. Suddenly plans for a career and family must take into account a disease whose course is uncertain. Yet many people with MS will continue to lead productive lives. A woman who has MS may still become pregnant and bear a child safely, although she may be instructed to discontinue her MS medications during pregnancy. And some of the physical limitations of the disease may make it more difficult for a mother with MS to care for her child.

Children whose parents have severe MS may find it hard to accept the changes they see happening in a person they remember as having been able to do everything and whom they still depend upon. They may feel guilty enjoying things like bike rides that their parent can no longer enjoy, or they may get frustrated having to help with simple things like fetching a glass of water or turning the radio up.

MS takes a tremendous emotional and financial toll on the entire family. Support groups and counseling may help MS patients, families, and friends to cope.

Book

Organizations

National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. The U.S. governments leading supporter of biomedical research on nervous systems disorders, including MS.http://www.ninds.nih.gov

National Multiple Sclerosis Society, 733 Third Avenue, New York, NY 10017. An organization that since 1946 has been dedicated to helping people with MS and finding a cure for it.http://www.nmss.org

Tutorials

“Multiple Sclerosis: Hope through Research.” An excellent guide to the disease for patients and their families.http://www.ninds.nih.gov

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multiple sclerosis

multiple sclerosis (MS) Incurable disorder of unknown cause in which there is degeneration of the myelin sheath that surrounds nerves in the brain and spinal cord. Striking mostly young adults, symptoms may include unsteadiness, loss of coordination, and speech and visual disturbances. MS sufferers typically have relapses and remissions over many years.

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multiple sclerosis

mul·ti·ple scle·ro·sis • n.
a chronic, typically progressive disease involving damage to the sheaths of nerve cells in the brain and spinal cord, whose symptoms may include numbness, impairment of speech and of muscular coordination, blurred vision, and severe fatigue.

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multiple sclerosis

multiple sclerosis A slowly progressive disease involving nerve degeneration; it may take many years to develop to the stage of paralysis, and it is subject to random periods of spontaneous remission. There is some evidence that supplements of polyunsaturated fatty acids slow its progression.

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